Director, Center for Tropical and Emerging Global Diseases
Professor, Dept. of Microbiology
Ph.D., 1968
Tulane University

RESEARCH

Our laboratory uses field, whole animal, cellular and molecular approaches to further an understanding of the immunobiology of experimental and clinical schistosomiasis. We have focused primarily on immunopathology and immunoregulation in these settings, but have also examined protective immune responses, and interactions between the immune system and eosinophils. Schistosomiasis is a parasitic worm infection that people acquire by going into fresh water that contains schistosome-infected snails, the intermediate host. Globally, about 200 million people are infected with this intravascular worm. Twenty million of those infected suffer severe, life-threatening disease, while another 100 million have other levels of morbidity due to their schistosomiasis, making it a major public health threat in endemic areas of the world. Schistosomes live for years inside the blood vessels of the 200 million people infected. There they produce large numbers of eggs, some of which are excreted out of the body to complete the life cycle, while others are retained in the liver and other organs, where they induce morbidity. Our research seeks to understand the roles of the immune system in the pathogenesis, regulation, and resistance observed during this chronic disease, and investigates how these findings can contribute to the control of its transmission and the widespread morbidity it causes. In addition, because of the chronic nature of schistosomiasis, a better understanding of the immune interactions in this setting may shed light on other chronic antigenic exposures, such as organ transplantation, autoimmune diseases and cancer. Our studies in Athens are done in a mouse/Schistosoma mansoni model. Our human studies of S. mansoni infections have been done through extensive collaborations in the West Indies, Brazil, Egypt and Kenya, with a current emphasis on Kenya.

In Kenya, we focus on the immune responses and epidemiology of people who are daily confronted with exposure to S. mansoni through their normal activities and occupations.

Our major research emphasis in all of these settings is to understand how the host and the parasite interact and counter-balance each other to establish stable, chronic, largely asymptomatic, infections. This relatively balanced situation is what occurs in most people harboring these organisms. Unfortunately, in a proportion of those infected, adverse outcomes occur, and result in severe morbidity and mortality. We want to determine the mechanisms responsible for these different outcomes. Our laboratory has described, and is defining the roles of suppressor T lymphocytes in the regulation of anti-egg granuloma formation and fibrosis. This seems to involve given idiotypic expression on some anti-schistosome antibodies, and anti-idiotypic T cell responses. The resulting regulatory events occur upon both chronic antigenic exposure and at the maternal/perinatal interface, and strongly influence the Th1 and Th2 cytokine profiles observed. Determination of the receptor/ligand and activation mechanisms responsible for these findings, and how to manipulate these interactions, is of high priority in our laboratory. In regard to anti-schistosome resistance mechanisms, we have, in Kenya, described the development of immune resistance in some people who are occupationally repeatedly exposed to schistosome infection and treated for their schistosomiasis. These observations will now be followed by establishing which immune response mechanisms correlate with resistance vs. continued susceptibility, and should contribute to the quest for a vaccine against schistosomiasis.

CONTACT INFORMATION

(706) 542-4112, dcolley@uga.edu

REPRESENTATIVE PUBLICATIONS

Montesano, M.A., D.G. Colley, S. Eloi-Santos, G.L. Freeman, Jr. and W.E. Secor. "Neonatal idiotypic exposure slaters subsequent cytokine, pathology and survival patterns in experimental Schistosoma mansoni infections." J. Exp. Med. 189:637-645, 1999.

Montesano, M.A., D.G. Colley, G.L. Freeman, Jr. and W.E. Secor. "Neonatal exposure to idiotype induces Schistosoma mansoni egg antigen specific cellular and humoral immune responses." J. Immunol. 163:898-905, 1999.

Lawn, S.D., D.M.S. Karanja, P. Mwinzi, J. Andove, D.G. Colley, T.M. Folks, and W.E. Secor. "The effect of treatment of schistosomiasis on blood plasma HIV-1 RNA concentration in coinfected individuals." AIDS 14:2437-2443, 2000.

Mwinzi, P.N.M., D.M.S. Karanja, D.G. Colley, A.S.S. Orago, and W.E. Secor. 2001. "Cellular immune responses of schistosomiasis patients are altered by Human Immunodeficiency Virus-1 co-infection." J. Inf. Dis. 184:488-496, 2001.

James, S.L. and D.G.Colley. "Progress in vaccine development." In: Schistosomiasis. Ed. A.A.F. Mahmoud, Imperial College Press, London, pp. 469-495, 2001.

Colley, D.G., P.T. LoVerde, and L. Savioli. "Medical helminthology in the 21st Century." Science 293:1437-1438, 2001

Mwinzi, P.N.M., Karanja, D.M.S., Kareko, I., Magak, P.W., Orago, A.S.S., Colley, D.G., and Secor, W.E. "Evaluation of hepatic fibrosis in persons co-infected with Schistosoma mansoni and human immunodeficiency virus-1." Am. J. Trop. Med. Hyg., 71:783-786, 2004.

Colley, D.G. and Secor, W.E. "Immunoregulation and World Health Assembly Resolution 54/19: Why does treatment control morbidity?" Parasitol International, 53:143-150, 2004.

Secor, W.E., Karanja, D.M., Colley, D.G. "Interactions between schistosomiasis and human immunodeficiency virus in Western Kenya." Mem. Inst. Oswaldo Cruz 99 (5 Suppl 1): 93-95, 2004.

Colley, D.G., Sasser, L.E. and Reed, A.M. "PD-L2+ dendritic cells and PD-1+ CD4+ T cells in schistosomiasis correlate with morbidity." Parasite Immunol., 27:45-53, 2005.

Beard, C.B., Fox, M.R., Lawrence.G.G., Guarner, J., Hanzlick, R.L., Huang, L., del Rio, C., Rimland, D., Duchin, J.S., and Colley, D.G. "Genetic differences in Pneumocystis isolates from immunocompetent infants and from adults with AIDS Epidemiological implications." J. Infect. Dis.,192:1815-1818, 2005.

Ganley-Leal, L.M., Mwinzi, P.N., Cetre-Sossah, C.B., Andove, J., Hightower, A.W., Karanja, D.M.S., Colley, D.G., and Secor, W.E. "The role of eosinophils in protection against infection with Schistosoma mansoni and the effect of HIV-1 co-infection in humans." Infect. Immunity, 74:2169-2176, 2006.

Secor, W. Evan and Colley, Daniel G. Schistosomiasis, World Class Parasites, Volume 10, Springer, New York, 2005.

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